The proposed work is focused on genetic studies of 2,3-diphospho-glycerate (DPG) levels in erythrocytes of rats, and to a lesser extent mice, and the relationship of a DPG locus and its alleles to a beta hemoglobin locus and its alleles. In one longstanding outbred population of rats, a single locus, polymorphic, two allele system with major effects of DPG levels exists. This DPG locus is linked to a polymorphic IIIB globin locus, and linkage disequilibrium is present, in spite of 200 generation existence of the population. The two main thrusts of the proposed work are first, to place the two DPG alleles on the same inbred genetic background. This will be done by either inbreeding our present rat lines by brother-sister inbreeding with heterozygosity forced by backcrossing, or developing a congenic line by placing the High DPG allele on a presently inbred Low DPG rat line. The latter approach must await genetic studies to confirm that the Low DPG phenotype in a given inbred line is due to an allelic difference at the same single major DPG locus. The availability of a segregating inbred or congenic line would allow important studies of the effects of variation in oxygenation to be done, since DPG differences cause hemoglobin oxygen affinity differences. The second main thrust is to study further the single locus genetic determination of differences in DPG levels among inbred lines, the generality of the linkage in relationship to the IIIB globin locus, and the generality of favored linkage phases. Similar work will be initiated among inbred lines of mice, since a linkage homology involves the beta globin locus exists between rats and mice, and we have already shown the existence of non-random relationships between beta globin alleles and DPG levels in inbred mouse lines.